Cancer and Inhalational Anesthesia

Inflammatory Biomarker Levels After Propofol or Sevoflurane Anesthesia: A Meta-analysis

Abbreviated Source

 Anesth Analg. 134(1):69-81, 2022 01 01.

Authors

 O'Bryan LJ; Atkins KJ; Lipszyc A; Scott DA; Silbert BS; Evered LA

Abstract

 BACKGROUND: The perioperative inflammatory response may be implicated in adverse outcomes including neurocognitive dysfunction and cancer recurrence after oncological surgery. The immunomodulatory role of anesthetic agents has been demonstrated in vitro; however, its clinical relevance is unclear. The purpose of this meta-analysis was to compare propofol and sevoflurane with respect to biomarkers of perioperative inflammation. The secondary aim was to correlate markers of inflammation with clinical measures of perioperative cognition.

  METHODS: Databases were searched for randomized controlled trials examining perioperative inflammation after general anesthesia using propofol compared to sevoflurane. Inflammatory biomarkers investigated were interleukin (IL)-6, IL-10, tissue necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP). The secondary outcome was incidence of perioperative neurocognitive disorders. Meta-analysis with metaregression was performed to determine the difference between propofol and sevoflurane.

  RESULTS: Twenty-three studies were included with 1611 participants. Studies varied by surgery type, duration, and participant age. There was an increase in the mean inflammatory biomarker levels following surgery, with meta-analysis revealing no difference in effect between propofol and sevoflurane. Heterogeneity between studies was high, with surgery type, duration, and patient age contributing to the variance across studies. Only 5 studies examined postoperative cognitive outcomes; thus, a meta-analysis could not be performed. Nonetheless, of these 5 studies, 4 reported a reduced incidence of cognitive decline associated with propofol use.

  CONCLUSIONS: Surgery induces an inflammatory response; however, the inflammatory response did not differ as a function of anesthetic technique. This absence of an effect suggests that patient and surgical variables may have a far more significant impact on the postoperative inflammatory responses than anesthetic technique. The majority of studies assessing perioperative cognition in older patients reported a benefit associated with the use of propofol; however, larger trials using homogenous outcomes are needed to demonstrate such an effect. Copyright © 2021 International Anesthesia Research Society.

Date of Publication

 2022 01 01

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Anesthesia and Long-term Oncological Outcomes: A Systematic Review and Meta-analysis

Abbreviated Source

 Anesth Analg. 132(3):623-634, 2021 03 01.

Authors

 Chang CY; Wu MY; Chien YJ; Su IM; Wang SC; Kao MC

Abstract

 BACKGROUND: Whether propofol elicits a survival benefit over volatile anesthetics during cancer surgery remains inconclusive. The primary aim of this systematic review and meta-analysis is to compare the effects of propofol-based total intravenous anesthesia (TIVA) with any volatile anesthesia on long-term oncological outcomes. The secondary aim is to compare propofol-based TIVA with specific volatile agents on long-term oncological outcomes.

  METHODS: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library from inception through March 3, 2020. Randomized control trials and observational studies that compared the effects of propofol-based TIVA and volatile anesthesia on long-term oncological outcomes, which also reported hazard ratios (HR) as effect estimates, were considered eligible for inclusion. Using the inverse variance method with a random-effects model, HR and 95% confidence intervals (CI) were calculated. Trial sequential analysis was incorporated to test if the results were subject to a type I or type II error.

  RESULTS: Nineteen retrospective observational studies were included. Patients who received propofol-based TIVA during cancer surgery were associated with significantly better overall survival than those who received volatile anesthesia (HR = 0.79, 95% CI, 0.66-0.94, P = .008, I2 = 82%). In contrast, no statistically significant difference was observed in recurrence-free survival between patients who received propofol-based TIVA and volatile anesthesia during cancer surgery (HR = 0.81, 95% CI, 0.61-1.07, P = .137, I2 = 85%). In the subgroup analysis by different volatile anesthetics, patients who received propofol-based TIVA were associated with better overall survival than those who received desflurane (HR = 0.54, 95% CI, 0.36-0.80, P = .003, I2 = 80%). In contrast, there was no statistically significant difference in overall survival between patients who received propofol-based TIVA and those who received sevoflurane (HR = 0.92, 95% CI, 0.74-1.14, P = .439, I2 = 70%). In the trial sequential analysis of overall survival, the cumulative Z curve reached the required heterogeneity-adjusted information size and crossed the traditional significance boundary. In contrast, in the trial sequential analysis of recurrence-free survival, the cumulative Z curve did not cross the traditional significance boundary. However, the required heterogeneity-adjusted information size has not yet been reached.

  CONCLUSIONS: Propofol-based TIVA is generally associated with better overall survival than volatile anesthesia during cancer surgery. Further large-scaled, high-quality randomized control trials are warranted to confirm our findings. Copyright © 2020 International Anesthesia Research Society.

Date of Publication

 2021 03 01

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Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia

Abbreviated Source

 Can J Anaesth. 66(5):546-561, 2019 May.

Authors

 Yap A; Lopez-Olivo MA; Dubowitz J; Hiller J; Riedel B

Abstract

 PURPOSE: Cancer-related mortality, a leading cause of death worldwide, is often the result of metastatic disease recurrence. Anesthetic techniques have varying effects on innate and cellular immunity, activation of adrenergic-inflammatory pathways, and activation of cancer-promoting cellular signaling pathways; these effects may translate into an influence of anesthetic technique on long-term cancer outcomes. To further analyze the effects of propofol (intravenous) and volatile (inhalational gas) anesthesia on cancer recurrence and survival, we undertook a systematic review with meta-analysis.

  SOURCE: Databases were searched up to 14 November 2018. Comparative studies examining the effect of inhalational volatile anesthesia and propofol-based total intravenous anesthesia (TIVA) on cancer outcomes were included. The Newcastle Ottawa Scale (NOS) was used to assess methodological quality and bias. Reported hazard ratios (HRs) were pooled and 95% confidence intervals (CIs) calculated.

  PRINCIPAL FINDINGS: Ten studies were included; six studies examined the effect of anesthetic agent type on recurrence-free survival following breast, esophageal, and non-small cell lung cancer (n = 7,866). The use of TIVA was associated with improved recurrence-free survival in all cancer types (pooled HR, 0.78; 95% CI, 0.65 to 0.94; P < 0.01). Eight studies (n = 18,778) explored the effect of anesthetic agent type on overall survival, with TIVA use associated with improved overall survival (pooled HR, 0.76; 95% CI, 0.63 to 0.92; P < 0.01).

  CONCLUSION: This meta-analysis suggests that propofol-TIVA use may be associated with improved recurrence-free survival and overall survival in patients having cancer surgery. This is especially evident where major cancer surgery was undertaken. Nevertheless, given the inherent limitations of studies included in this meta-analysis these findings necessitate prospective randomized trials to guide clinical practice.

  TRIAL REGISTRATION: PROSPERO (CRD42018081478); registered 8 October, 2018.

Date of Publication

 2019 May

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Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial

Abbreviated Source

 Lancet. 394(10211):1807-1815, 2019 11 16.

Authors

 Sessler DI; Pei L; Huang Y; Fleischmann E; Marhofer P; Kurz A; Mayers DB; Meyer-Treschan TA; Grady M; Tan EY; Ayad S; Mascha EJ; Buggy DJ

Abstract

 BACKGROUND: Three perioperative factors impair host defence against recurrence during cancer surgery: the surgical stress response, use of volatile anaesthetic, and opioids for analgesia. All factors are ameliorated by regional anaesthesia-analgesia. We tested the primary hypothesis that breast cancer recurrence after potentially curative surgery is lower with regional anaesthesia-analgesia using paravertebral blocks and the anaesthetic propofol than with general anaesthesia with the volatile anaesthetic sevoflurane and opioid analgesia. A second hypothesis was that regional anaesthesia-analgesia reduces persistent incisional pain.

  METHODS: We did a randomised controlled trial at 13 hospitals in Argentina, Austria, China, Germany, Ireland, New Zealand, Singapore, and the USA. Women (age <85 years) having potentially curative primary breast cancer resections were randomised by computer to either regional anaesthesia-analgesia (paravertebral blocks and propofol) or general anaesthesia (sevoflurane) and opioid analgesia. The primary outcome was local or metastatic breast cancer recurrence. The secondary outcome was incisional pain at 6 months and 12 months. Primary analyses were done under intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT00418457. The study was stopped after a preplanned futility boundary was crossed.

  FINDINGS: Between Jan 30, 2007, and Jan 18, 2018, 2132 women were enrolled to the study, of whom 24 were excluded before surgery. 1043 were assigned to regional anaesthesia-analgesia and 1065 were allocated to general anaesthesia. Baseline characteristics were well balanced between study groups. Median follow-up was 36 (IQR 24-49) months. Among women assigned regional anaesthesia-analgesia, 102 (10%) recurrences were reported, compared with 111 (10%) recurrences among those allocated general anaesthesia (hazard ratio 0.97, 95% CI 0.74-1.28; p=0.84). Incisional pain was reported by 442 (52%) of 856 patients assigned to regional anaesthesia-analgesia and 456 (52%) of 872 patients allocated to general anaesthesia at 6 months, and by 239 (28%) of 854 patients and 232 (27%) of 852 patients, respectively, at 12 months (overall interim-adjusted odds ratio 1.00, 95% CI 0.85-1.17; p=0.99). Neuropathic breast pain did not differ by anaesthetic technique and was reported by 87 (10%) of 859 patients assigned to regional anaesthesia-analgesia and 89 (10%) of 870 patients allocated to general anaesthesia at 6 months, and by 57 (7%) of 857 patients and 57 (7%) of 854 patients, respectively, at 12 months.

  INTERPRETATION: In our study population, regional anaesthesia-analgesia (paravertebral block and propofol) did not reduce breast cancer recurrence after potentially curative surgery compared with volatile anaesthesia (sevoflurane) and opioids. The frequency and severity of persistent incisional breast pain was unaffected by anaesthetic technique. Clinicians can use regional or general anaesthesia with respect to breast cancer recurrence and persistent incisional pain.

  FUNDING: Sisk Healthcare Foundation (Ireland), Eccles Breast Cancer Research Fund, British Journal of Anaesthesia International, College of Anaesthetists of Ireland, Peking Union Medical College Hospital, Science Fund for Junior Faculty 2016, Central Bank of Austria, and National Healthcare Group. Copyright © 2019 Elsevier Ltd. All rights reserved.

Date of Publication

 2019 11 16

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Effect of Equipotent Doses of Propofol versus Sevoflurane Anesthesia on Regulatory T Cells after Breast Cancer Surgery

Abbreviated Source

 Anesthesiology. 129(5):921-931, 2018 11.

Authors

 Oh CS; Lee J; Yoon TG; Seo EH; Park HJ; Piao L; Lee SH; Kim SH

Abstract

 WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Clusters of differentiation 39 and 73, enzymes expressed on the surface of regulatory T cells, promote cancer recurrence and metastasis by suppressing immune cells. The authors hypothesized that propofol is less immunosuppressive than volatile anesthetics. The objective of this randomized trial was to compare the changes in cluster of differentiation 39 and 73 expression on regulatory T cells between propofol- and sevoflurane-based anesthesia during breast cancer surgery.

  METHODS: A total of 201 patients having breast cancer surgery were randomly assigned and analyzed (n = 99 for propofol, n = 102 for sevoflurane). Blood samples were obtained immediately before anesthesia induction and 1 and 24 h postoperatively. The frequency of cluster of differentiation 39 and 73 expression on circulating regulatory T cells (primary outcome) and the frequency of circulating type 1 and type 17 helper T cells, natural killer cells, and cytotoxic T cells were investigated. Serum cytokines and the neutrophil-to-lymphocyte ratio were also evaluated.

  RESULTS: Changes in cluster of differentiation 39 and 73 expression on regulatory T cells over time did not differ with propofol and sevoflurane groups (difference [95% confidence interval]: 0.01 [-2.04 to 2.06], P = 0.995 for cluster of differentiation 39; -0.93 [-3.12 to 1.26], P = 0.403 for cluster of differentiation 73). There were no intergroup differences in type 1, type 17 helper T cells, natural killer cells, cytotoxic T cells, cytokines, or the neutrophil-to-lymphocyte ratio.

  CONCLUSIONS: Changes in immune cells were similar with propofol and sevoflurane during breast cancer surgery. The effect of anesthetics on the perioperative immune activity may be minimal during cancer surgery.

Date of Publication

 2018 11

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The Effects of Perioperative Anesthesia and Analgesia on Immune Function in Patients Undergoing Breast Cancer Resection: A Prospective Randomized Study

Abbreviated Source

 Int J Med Sci. 14(10):970-976, 2017.

Authors

 Cho JS; Lee MH; Kim SI; Park S; Park HS; Oh E; Lee JH; Koo BN

Abstract

 Introduction: Perioperative anesthesia and analgesia exacerbate immunosuppression in immunocompromised cancer patients. The natural killer (NK) cell is a critical part of anti-tumor immunity. We compared the effects of two different anesthesia and analgesia methods on the NK cell cytotoxicity (NKCC) in patients undergoing breast cancer surgery. Methods: Fifty patients undergoing breast cancer resection were randomly assigned to receive propofol-remifentanil anesthesia with postoperative ketorolac analgesia (Propofol-ketorolac groups) or sevoflurane-remifentanil anesthesia with postoperative fentanyl analgesia (Sevoflurane-fentanyl group). The primary outcome was NKCC, which was measured before and 24 h after surgery. Post-surgical pain scores and inflammatory responses measured by white blood cell, neutrophil, and lymphocyte counts were assessed. Cancer recurrence or metastasis was evaluated with ultrasound and whole body bone scan every 6 months for 2 years after surgery. Results: The baseline NKCC (%) was comparable between the two groups (P = 0.082). Compared with the baseline value, NKCC (%) increased in the Propofol-ketorolac group [15.2 (3.2) to 20.1 (3.5), P = 0.048], whereas it decreased in the Sevoflurane-fentanyl group [19.5 (2.8) to 16.4 (1.9), P = 0.032]. The change of NKCC over time was significantly different between the groups (P = 0.048). Pain scores during 48 h after surgery and post-surgical inflammatory responses were comparable between the groups. One patient in the Sevoflurane-fentanyl group had recurrence in the contralateral breast and no metastasis was found in either group. Conclusions: Propofol anesthesia with postoperative ketorolac analgesia demonstrated a favorable impact on immune function by preserving NKCC compared with sevoflurane anesthesia and postoperative fentanyl analgesia in patients undergoing breast cancer surgery.

Date of Publication

 2017

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Thoracic paravertebral regional anesthesia improves analgesia after breast cancer surgery: a randomized controlled multicentre clinical trial

Abbreviated Source

 Can J Anaesth. 62(3):241-51, 2015 Mar.

Authors

 Wu J; Buggy D; Fleischmann E; Parra-Sanchez I; Treschan T; Kurz A; Mascha EJ; Sessler DI

Abstract

 BACKGROUND: The contribution of regional anesthesia with thoracic paravertebral blockade to postoperative analgesia remains unclear. We compared the effect of a combination of paravertebral blockade and propofol general anesthesia (GA) with sevoflurane GA and opioid analgesia on postoperative pain and opioid use for patients undergoing breast cancer surgery.

  METHODS: Patients having breast cancer surgery were randomly assigned to paravertebral analgesia with propofol GA (PPA, n = 187) or sevoflurane GA with perioperative opioid analgesia (SOA, n = 199). The PPA and SOA groups were compared for opioid consumption and pain outcomes (on a 0-10 visual analogue scale [VAS]) at two hours postoperatively using superiority and inferiority statistics. We compared our results with previous publications in a meta-analysis.

  RESULTS: Compared with the SOA group, the PPA group experienced reduced median [interquartile range] pain VAS scores (1 [1,3] vs 2.5 [1,4], respectively; median difference -1.0; 99% confidence intervals [CI]: -1.5 to -0.5) and required less intraoperative fentanyl (50 [0, 125] microg vs 200 [100, 300] microg, respectively; median difference -100; 99% CI: -150 to -100) and less long-acting opioid (0 [0, 0] mg vs 3.0 [0, 12] mg, respectively, morphine equivalents; median difference -3; 99% CI: -4 to -2). Thus, non-inferiority was detected for all the above outcomes, and superiority tests for each outcome were highly significant in the expected directions (P < 0.001). Meta-analysis, including the current study, estimated a reduction in worst pain of 2.3 points (95% CI: 1.8 to 2.8) on a 0-10 scale and a 72% reduction (95% CI: 42 to 87) in mean opioid consumption in the immediate two postoperative hours for PPA vs SOA.

  CONCLUSION: Our results were largely consistent with previous much smaller studies. Compared with sevoflurane GA with opioid analgesia, the combination of paravertebral analgesia with propofol GA provides an early clinical analgesic benefit in females having breast cancer surgery. This analysis is a substudy of an ongoing multicentre double-blinded randomized trial ( www.clinicaltrials.gov , NCT00418457) of cancer recurrence.

Date of Publication

 2015 Mar

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